Tangential Flow Filtration (TFF) Technology

Tangential flow filtration (TFF) is one of the key technologies used to purify and concentrate target proteins in downstream processing of protein-based biopharmaceuticals. This technology can gently and efficiently process large amounts of protein solutions while minimizing sample loss and maintaining the integrity of sensitive molecules. CD Formulation integrates cutting-edge TFF technology into our protein characterization technology platform to provide reliable analytical support for the downstream process development of your protein/peptide drugs.

What is Tangential Flow Filtration (TFF) Technology?

TFF, also known as cross-flow filtration, is an important technology in bioprocessing and purification that can be used to separate, concentrate, and purify biomolecules such as proteins, enzymes, viruses, and cells. This technology is a method that uses ultrafiltration membranes to quickly and efficiently separate and purify biomolecules. Unlike traditional filtration methods that use filters to directly capture particles or solutes, TFF uses a flow path design that allows the liquid flow to flow tangentially to the surface of the filter membrane instead of passing through the membrane vertically, which would clog the filter media. This method is favored for its continuous filtration and reproducible performance.

Fig. 1 A schematic illustration of a tangential flow filtration system. (Visan KS, et al., 2022)

When Do You Need Tangential Flow Filtration (TFF) Technology?

In the downstream processing of protein biopharmaceuticals, TFF technology is mainly used for the concentration and diafiltration of target protein or peptide molecules.

• Concentration: The concentration of the solution is increased by removing liquid through TFF technology while retaining protein or peptide molecules. This process uses a membrane with a specific molecular weight cutoff (MWCO) to selectively retain the target protein or peptide molecules while allowing small molecule impurities, salts, and water to be removed through the membrane.
• Diafiltration: Focuses on separating particles of different sizes through TFF technology. By selecting the appropriate membrane, efficient separation of small particles (such as salts, fillers, etc.) and large particles (such as target protein or peptide molecules) can be achieved.

Our Services Related to Tangential Flow Filtration (TFF)

Thanks to decades of experience supporting protein/peptide biopharmaceutical development and manufacturing using TFF technology, our team of highly qualified experts offers a range of TFF-related services to accelerate the implementation and success of your project.

Our experienced team of experts has completed hundreds of TFF separation and purification projects for protein and peptide, supporting all stages of your protein/peptide drug development and manufacturing - from early studies to downstream process monitoring and GMP batch release testing.

Utilizing cutting-edge TFF technology, we support the following protein/peptide development and characterization plans, including but not limited to:

• Purification and/or recovery of recombinant proteins from cell culture media.
• Separation of protein mixtures.
• Concentration and desalting of proteins and peptides.
• Cell harvesting (bacteria, yeast, mammalian cells.).
• Concentration of plasmid DNA and exchange of chromatography buffer to final buffer during plasmid DNA manufacturing for protein production.
• Pre-concentration of therapeutic proteins prior to anion exchange chromatography.
• Pre-filtration components of WFI systems for endotoxin removal.
• Recovery of bacterial cultures and viruses.
• Removal of PVA excreted from excipients of nanoparticles during drug loading.
• Preparation of samples for chromatographic analysis.

How We Design The Best TFF System for You?

The membrane structure designed for the TFF system is very different from the membrane structure used in direct flow filtration. Throughout the TFF system design process, our team of process development experts focuses on the following factors to solve any possible challenges you may have.

Size of Target Protein or Peptide Molecule

This can be defined by molecular weight or size. Generally, when separating by molecular weight, we will choose a membrane that is 1/6 to 1/3 smaller than the target molecule, while when separating by molecular size, we will choose a membrane with a pore size smaller than the target molecule.

Retain or Remove Target Molecule (Target Protein/Peptide or Impurity)

Our scientists will customize the design according to your needs. For components that need to be retained, concentration is the best, while for components that need to be removed, dialysis, desalting, and buffer exchange are our important strategies.

Recovery of Target Protein or Peptide

Recovery is related to molecular weight cutoff (MWCO). We will screen the best filtration membrane based on your recovery needs. If a lower recovery rate is acceptable, a membrane with a MWCO of 1/3 of the target molecule will help speed up the recovery process. If higher recovery is required, membranes with MWCO as low as 1/6 are your best choice.

Available Types of Tangential Flow Filtration (TFF) Analysis

We provide you with professional protein/peptide downstream processing services using the following two TFF analysis technologies. The main difference between these two TFFs is the number of passes of the feed solution.

Single-Pass TFF

In a single-pass TFF process, the liquid passes through the membrane element in a tangential flow. The required protein concentration or buffer exchange occurs in a single pass, which can be achieved by adjusting the TMP or increasing the residence time in the filter. This approach usually improves separation efficiency and reduces membrane fouling.

Traditional Batch TFF

In traditional TFF, the feed solution passes through the filter multiple times, and the buffer composition in the feed solution is changed to concentrate the protein solution. This is because the filters used in traditional TFF usually allow higher feed flux, resulting in increased sweep rate and shortened residence time, thus requiring multiple passes.

Fig. 2 Schematic of a) traditional TFF and b) SP-TFF setup. (S Malladi, et al., 2023)

Advantages of Tangential Flow Filtration (TFF) Technology

• Easy to use.
• Efficient, fast, and scalable.
• TFF can be run at lower pressures than traditional filtration methods, which reduces costs.
• The cross-flow nature of TFF allows for high flow rates of feed solutions, which reduces processing time compared to traditional dead-end filtration systems.
• Operates continuously, allowing for rapid separation and purification of protein/peptide molecules.
• TFF systems can be easily scaled up or down, making them suitable for both small-scale laboratory work and large-scale industrial applications.
• The flow in a TFF system is tangential to the membrane surface, solids, and other particulates are continuously removed from the membrane, minimizing the fouling that can occur in normal filtration.

Custom Tangential Flow Filtration (TFF) Services

Why Choose Our Tangential Flow Filtration (TFF) Technology?

• Our dedicated team of experts boasts extensive experience in TFF analytical method development and validation, ensuring that your processes are robust, reliable, and meet regulatory standards.
• We have accumulated decades of expertise and successful project experience using TFF technology to support protein/peptide biopharmaceutical development. Our track record demonstrates our capability in addressing complex challenges and achieving efficient, high-quality production outcomes.
• We leverage the latest advancements in TFF technology to provide innovative solutions that enhance your workflow, improve yield, and reduce process times, all while maintaining the integrity of your biopharmaceutical products.
• Our TFF technology is designed to be scalable, allowing you to seamlessly transition from research and development to commercial production.
• We adhere to strict quality control and regulatory standards to ensure the integrity and compliance of your data.
• We provide flexible experimental design and customized solutions.

Publication

CD Formulation aims to provide a powerful analytical tool for the separation, purification, and characterization of proteins and peptides. Please feel free to contact us if you are interested in our services. Learn how our TFF technology can support the smooth implementation of your protein/peptide biopharmaceutical program.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.